The unusual transmission genetics of RNA viruses pose unique opportunities for the design of anti-viral compounds. High polymerase error rates lead to high variability in the population of RNA genomes. However, the polyploid nature of viral infections leads to variations in selection pressure on different regions of RNA genomes, the consequences of which are unexplored. I hypothesize that differences in selection pressures will lead to differences in the observed rates of reversions of lethal mutations depending on the genetic behavior of the encoded viral product. Using poliovirus as a model system, a method to map reversion rates across the viral genome will be developed. The goal of this work is to produce a general method to map reversion rates for any positive-strand RNA virus, to identify regions of the genome likely to encode cis-acting RNAs and proteins, trans-acting monomers, or trans-acting oligomeric proteins, and to locate genetically stable elements of the viral genome for targeting by anti-viral compounds. If the predicted differences in reversion rates are found, the same method will be applied to bovine viral diarrhea virus (BVDV), a homolog of hepatitis C virus (HCV). Finally, the effects of anti-viral compounds on the evolution and replication of these viruses will be tested.